Ronald M V Mota1, Henry Mankin. 1. Department of Pediatric Orthopedics, Socor Hospital, Belo Horizonte, Brazil.
Abstract
BACKGROUND: Gaucher disease is the most common lysosomal storage disease and is caused by deficient production and activity of the lysosomal enzyme beta-glucosidase (glucocerebrosidase), resulting in progressive accumulation of glucosylceramide (glucocerebroside) in lysosomes of cells of the reticuloendothelial system in the spleen, liver, and marrow. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone complications, including bone pain, bone marrow infiltration, lytic lesions, osteopenia, pathological fractures, and avascular necrosis. Early, adequate, and sustained treatment with enzyme replacement therapy (ERT) available since 1991 can change the natural history of the disease, particularly in children. Skeletal complications are usually the major source of disease morbidity and disability and although magnetic resonance imaging and dual-energy x-ray absorptiometry densitometry are recommended for monitoring, these are not readily available in all countries. METHODS: We describe 18 Brazilian children with type 1 Gaucher disease with bone involvement who were followed with plain radiography for at least 8 months after beginning imiglucerase ERT (initial dose, 15-60 U/kg body weight/15 days). Bone involvement noted by plain radiograph included marrow infiltration, osteopenia, pathological fractures, osteonecrosis, lytic lesions, and Erlenmeyer flask deformity. Patients were questioned about bone crises. RESULTS: Patients were followed for up to 10 years (mean follow-up, 4 years and 4 months +/- 3 years and 3 months). Bone changes were visible by plain radiographs in all patients. Clinical and radiological improvement was noted in 13 (72%) of 18 patients; bone lesions worsened in 5 (28%) of 18 patients. The final ERT dose for the 13 patients who improved was 55 +/- 10 U/kg (range, 30-60 U/kg), and the final ERT dose for the 5 who worsened was 29 +/- 2 U/kg (range, 26-30 U/kg); this difference was statistically significant (P < 0.03). CONCLUSIONS: When other imaging technologies are not available, skeletal response to ERT in children with type 1 Gaucher disease can be monitored effectively by plain radiography. Higher doses of ERT (50-60 U/kg /15 days) may be required for improvement of skeletal manifestations. CLINICAL EVIDENCE: Case series; level 4.
BACKGROUND: Gaucher disease is the most common lysosomal storage disease and is caused by deficient production and activity of the lysosomal enzyme beta-glucosidase (glucocerebrosidase), resulting in progressive accumulation of glucosylceramide (glucocerebroside) in lysosomes of cells of the reticuloendothelial system in the spleen, liver, and marrow. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone complications, including bone pain, bone marrow infiltration, lytic lesions, osteopenia, pathological fractures, and avascular necrosis. Early, adequate, and sustained treatment with enzyme replacement therapy (ERT) available since 1991 can change the natural history of the disease, particularly in children. Skeletal complications are usually the major source of disease morbidity and disability and although magnetic resonance imaging and dual-energy x-ray absorptiometry densitometry are recommended for monitoring, these are not readily available in all countries. METHODS: We describe 18 Brazilian children with type 1 Gaucher disease with bone involvement who were followed with plain radiography for at least 8 months after beginning imiglucerase ERT (initial dose, 15-60 U/kg body weight/15 days). Bone involvement noted by plain radiograph included marrow infiltration, osteopenia, pathological fractures, osteonecrosis, lytic lesions, and Erlenmeyer flask deformity. Patients were questioned about bone crises. RESULTS: Patients were followed for up to 10 years (mean follow-up, 4 years and 4 months +/- 3 years and 3 months). Bone changes were visible by plain radiographs in all patients. Clinical and radiological improvement was noted in 13 (72%) of 18 patients; bone lesions worsened in 5 (28%) of 18 patients. The final ERT dose for the 13 patients who improved was 55 +/- 10 U/kg (range, 30-60 U/kg), and the final ERT dose for the 5 who worsened was 29 +/- 2 U/kg (range, 26-30 U/kg); this difference was statistically significant (P < 0.03). CONCLUSIONS: When other imaging technologies are not available, skeletal response to ERT in children with type 1 Gaucher disease can be monitored effectively by plain radiography. Higher doses of ERT (50-60 U/kg /15 days) may be required for improvement of skeletal manifestations. CLINICAL EVIDENCE: Case series; level 4.